The pathogenesis of acne vulgaris is believed to involve follicular hyperkeratinization, elevated sebum production and hydrolysis of sebum triglycerides to free fatty acids by follicular bacteria. In addition, the sebum of acne patients contains a lower concentration of linoleic acid than normal. We propose to determine the cause and significance of the low linoleic acid levels in acne with the expectation that this might lead to preventive measures. The dienoic, trienoic and tetraenoic components will be separated from the methyl esters of sebum fatty acids by silver nitrate chromatography and the amounts and positions of unsaturation will be determined by gas chromatography. Quantities of specific polyunsaturated fatty acids will be correlated with the presence of acne and with the composition of systemic lipids to determine whether a general or localized essential fatty acid deficiency is responsible for follicular hyperkeratinization. The dynamics of sebum biosynthesis and excretion will be studied in vivo by measurement of the sebum content of biopsy specimens of skin and the numbers and dimensions of pilosebaceous follicles. Rates of sebum excretion per follicle in acne patients and normal subjects will be compared. The natural substrates for sebum biosynthesis and the mechanisms by which they are incorporated into sebum will be investigated by use of radioisotopic precursors in vivo and in vitro, especially with regard to formation of polyunsaturated fatty acids and branched chain compounds. The pathways of biosynthesis of the major lipid classes in sebum and how these are regulated by drugs will also be studied in vivo and in vitro. Measurements of surface excretion of sebum will be used to assess the effects of steroidal hormones and other drugs on sebum production and acne. It will also be determined to what extent antibiotics affect the bacterial populations and free fatty acid concentrations in comedones and how these parameters are related to clinical changes in acne.